Main Index   Search   Register   Login   Who's Online   FAQ   Links
  1 Online, 0 Active   You are not logged in  
Main Index     The HIVE light edition (TM)
This is a historical archive
The forum is read-only. Private information has been removed. It is not possible to login.


Tryptamine Chemistry Thread:   Previous  Forum index  Next

All 8 posts   Subject: New LSD analogs from the Nichols Lab   Please login to post   Down

 
    Rhodium
(Chief Bee)
09-06-02 07:02
No 353379
User Picture 
      New LSD analogs from the Nichols Lab
(Rated as: excellent)
    

Lysergamides of Isomeric 2,4-Dimethylazetidines Map the Binding Orientation of the Diethylamide Moiety in the Potent Hallucinogenic Agent N,N-Diethyllysergamide (LSD)

J. Med. Chem., 45 (19), 4344-4349 (2002)

Lysergic acid amides were prepared from (R,R)-(-)-, (S,S)-(+)-, and cis-2,4-dimethyl azetidine. The dimethylazetidine moiety is considered here to be a rigid analogue of diethylamine, and thus, the target compounds are all conformationally constrained analogues of the potent hallucinogenic agent, N,N-diethyllysergamide, LSD-25. Pharmacological evaluation showed that (S,S)-(+)-2,4-dimethylazetidine gave a lysergamide with the highest LSD-like behavioral activity in the rat two lever drug discrimination model that was slightly more potent than LSD itself. This same diastereomer also had the highest affinity and functional potency at the rat serotonin 5-HT2A receptor, the presumed target for hallucinogenic agents, and a receptor affinity profile in a panel of screens that was most similar to that of LSD itself. Both cis- and the (R,R)-trans-dimethylazetidines gave lysergamides that were less potent in all relevant assays. The finding that the S,S-dimethylazetidine gave a lysergamide with pharmacology most similar to LSD indicates that the N,N-diethyl groups of LSD optimally bind when they are oriented in a conformation distinct from that observed in the solid state by X-ray crystallography. The incorporation of isomeric dialkylazetidines into other biologically active molecules may be a useful strategy to model the active conformations of dialkylamines and dialkylamides.

https://www.rhodium.ws/pdf/azetidine-lsd.pdf
 
 
 
 
    foxy2
(Distinctive Doe)
09-06-02 12:54
No 353456
      Hmmmm     

I smell an interesting DET analog.
Indole-ethylbromide plus 2,4-dimethylazetidine.

Only thing is those damn pyr-T experiences worry me a bit.

Those who give up essential liberties for temporary safety deserve neither liberty nor safety
 
 
 
 
    zibarium
(Naked)
09-12-02 15:27
No 355636
      if rats could talk     

two-levered rat discrimination tests sound as if they might miss some of the more subjective aspects of a compound's attributes.

i wonder if these 'experienced rats' still prefer crack after a glimpse of the rat god-head?
 
 
 
 
    Cyrax
(Hive Bee)
09-12-02 16:48
No 355652
      Nice, they use the pyBOP coupling reagent, which ...     

Nice, they use the pyBOP coupling reagent, which is frequently used in peptide chemistry to couple amino acids.

pyBOP reacts with the acid to give an acyloxyphosphonium salt and the amine reacts with this intermediate to give the end product.

As a side note, pyBOP is used in place of BOP, since BOP yields the carcinogenic HMPT as a side product.

Those phosphonium coupling reagentia give better yields than DCC (dicyclohexylcarbodiimide).
 
 
 
 
    neuromodulator
(Hive Bee)
09-23-02 00:51
No 359276
      Ok but...     

Could you draw some structures for what ole St. Nick is up to?  Those words were German to me.  Furthermore, is LSD 025 (T26) not potent enough as it is.  I'll stick with ETH-LAD.
 
 
 
 
    Rhodium
(Chief Bee)
09-23-02 04:39
No 359369
User Picture 
      Click the link in my post for a structuran ...     

Click the link in my post for a structural formula.
 
 
 
 
    TheRampartLion11
09-23-02 14:18
      My computer wouldn't allow it.
(Rated as: insignificant)
    
 
 
 
    Rhodium
(Chief Bee)
10-21-04 14:23
No 536964
User Picture 
      Dave Nichols' Essays from the Heffter Review
(Rated as: excellent)
    

LSD and Its Lysergamide Cousins
David E. Nichols
The Heffter Review of Psychedelic Research, Vol. 2, pp. 80-87 (2001) (https://www.rhodium.ws/pdf/nichols/nichols-lsd.lysergamide.cousins.pdf)
____ ___ __ _

The Medicinal Chemistry of Phenethylamine Psychedelics
David E. Nichols
The Heffter Review of Psychedelic Research, Vol. 1, pp. 40-45 (1998) (https://www.rhodium.ws/pdf/nichols/nichols-pea.medicinal.chemistry.pdf)

The Hive - Clandestine Chemists Without Borders
 
 

All 8 posts   End of thread   Top
   

 https://the-hive.archive.erowid.org    the-hive@erowid.org
   
Powered by Chemical Revolution v1.4, 2022-2023, Living Light Research Europe

Links     Erowid     Rhodium

PIHKAL     TIHKAL     Total Synthesis II

Date: 06-21-24, Release: 1.6 (10-04-15), Links: static, unique